Tumors are highly heterogeneous tissues at multiple levels. This makes molecular analysis of tumors difficult, which in turn limits pathological (differential) diagnosis and the assignation of effective treatments. Solid tumors develop in a complex microenvironment comprised of epithelial cells, immune cells, fibroblasts, and others. The relationships between these cell types can have multiple levels. Infiltrating immune cells may initially destroy neoplastic cells. However, chronic inflammation, an innate immune response, has an indispensable role in promoting tumor growth and metastasis. Understanding tumor-immune interactions thus has profound clinical implications. The proposed research aims to develop integrated microchips to address this problem on multiple levels. The chips are designed to assay a large protein biomarker panel from tissue sample sizes varying from a finger prick of blood or a skinny needle biopsy, to a single cell. This technology permits for the direct addressing of the heterogeneous nature of tumors, and it can also serve as a clinical tool that exhibits dramatic performance benefits over existing approaches. For example, blood analysis chips are designed for the on-chip separation of plasma from whole blood, followed by assay of a large panel of protein biomarkers, all in a few minutes. These cost-effective chips will be used to measure a large pool of samples from cancer patients, and search for disease specific blood fingerprints. A similar platform, but harnessed as a single-cell analysis chip, permits for an array of secreted proteins to be assayed as a tumor is constructed, on chip, one cell at a time. This microchip will be harnessed to measure the function of different immune cells to delineate the complex cell-cell signaling networks within the tumor microenvironment and other inflammatory diseases, and it will also be utilized to measure anti-cancer drug responses in vitro. RELEVANCE: The proposed research has the potential to develop a practical clinical tool to differentially diagnose cancer through tumor-immune interactions. It can be executed inexpensively, non-invasively, informatively in not only clinical laboratories but also in the patient's home. This will help transform cancer diagnosis and treatment from reactive to preventative and personalized.